AB0013 LONGITUDINAL CHANGES IN VARICELLA ZOSTER VIRUS (VZV)-SPECIFIC T CELL IMMUNITY IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH DIFFERENT JAK INHIBITORS
Authors: S. Moustafa, C. G. Gialouri, K. Thomas, C. Koutsianas, C. Tsalapaki, A. Panagiotopoulos, E. Mavrea, K. Antonatou, E. Hadziyannis, D. Vassilopoulos
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Targeted synthetic agents such as the JAK inhibitors (JAKi) used for the treatment of various inflammatory diseases, including rheumatoid arthritis (RA), have been associated with increased risk for VZV reactivation and herpes zoster (HZ). Although this has been attributed to decreased T cell surveillance of latent VZV, detailed data on the effect of the different JAKi on VZV-specific T cell immunity are limited. <h3>Objectives</h3> To study longitudinally the kinetics of VZV-specific T cells in RA patients treated with different JAKi (baricitinib-BARI, tofacitinib-TOFA, upadacitinib-UPA) or methotrexate (MTX, control group). <h3>Methods</h3> Peripheral blood mononuclear cells (PBMCs) were isolated from RA patients before and after 4 and 12 weeks of treatment with JAKi or MTX. PBMCs were stimulated <i>in vitro</i> for 18 hours either specifically with VZV antigen (VZV lysate) or non-specifically with a polyclonal stimulus (Staphylococcus aureus enterotoxin B, SEB) and anti-CD28/49d. The percentage of CD4<sup>+</sup>CD69<sup>+</sup> effector T cells as well as of VZV specific CD4<sup>+</sup>CD69<sup>+</sup> T cells expressing IFNγ were measured by flow cytometry. <h3>Results</h3> 22 patients with active RA were included; 16 were treated with JAKi (BARI n=7, TOFA n=4, UPA n=5) and 6 with MTX. For the JAKi group, 88% were females with median age and disease duration of 62 and 8 years, respectively, and mean baseline DAS28-ESR of 5.6, while in the MTX group, 100% were females with median age and disease duration of 57 and 0.5 years and mean DAS28-ESR of 5, respectively. Treatment with JAKi for 12 weeks did not change significantly the % of the overall population of CD4<sup>+</sup>CD69<sup>+</sup> T cells stimulated i<i>n vitro</i> with VZV or SEB (p=0.3). Similarly, there was no significant change in the % of SEB-stimulated CD4<sup>+</sup>CD69<sup>+</sup>IFNγ<sup>+</sup> T cells between pre-treatment and after 12 weeks of JAKi treatment (median, from 0.1% to 0.075%, p=0.370, Figure 1a). In contrast, there was a significant decrease in VZV-specific CD4<sup>+</sup>CD69<sup>+</sup>IFNγ<sup>+</sup> T cells between these 2 time points (median, from 0.049% to 0.01%, p&lt;0.001, Figure 1b). The decrease in VZV-specific T cells was similar between the 3 different JAKi (Figure 1c). Patients treated with MTX (n=6) had a slight decrease in VZV specific T cells, but this did not reach the statistical significance (p=0.5). <h3>Conclusion</h3> Treatment of RA patients for 12 weeks with JAKi significantly reduced VZV-specific T cells without affecting the overall effector T cell population. The effect on VZV specific T cell immunity was similar with the 3 different JAKi. These preliminary findings provide novel information regarding the effect of JAKi on VZV-specific T cell immunity. <h3>Reference</h3> [1]Yun H. et al. Risks of herpes zoster in patients with rheumatoid arthritis according to biologic disease- modifying therapy. Arthritis Care Res. 2015;67(5):731–6 <h3>Acknowledgements</h3> Supported in part by the Special Account for Research Grants (S.A.R.G.), National and Kapodistrian University of Athens, Greece (DV #12085, 12086). <h3>Disclosure of Interests</h3> None Declared.